Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction

2007 ◽  
Vol 292 (3) ◽  
pp. F921-F929 ◽  
Author(s):  
Anni Eskild-Jensen ◽  
Klaus Thomsen ◽  
Christine Rungø ◽  
Luis S. Ferreira ◽  
Lene Fogt Paulsen ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Fractional Excretion ◽  
At1 Receptor ◽  
Receptor Blockade ◽  
Glomerular Function ◽  
Contralateral Kidney ◽  
Diagnostic Potential ◽  
Fractional Excretion Of Sodium ◽  
Renal Sodium Handling ◽  
Immunohistochemical Analyses

Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal function and in the present study we examined the effects of chronic AT1 receptor blockade using CV-11974 (0.12 mg/h candesartan from age 23 to 30 days) on kidney function development after PUUO was induced in 2-day-old piglets. Moreover, the effect of superimposed acute NO inhibition using NG-nitro-l-arginine methyl ester (l-NAME; 15 mg/kg) was examined to identify if this has diagnostic potential. PUUO significantly increased GFR in the nonobstructed contralateral kidney independent of candesartan. In candesartan-treated piglets, the l-NAME-induced GFR reduction seen in normal and nonobstructed kidneys was absent in the partial obstructed kidneys. Urine output and fractional excretion of water were increased from the partial obstructed kidneys. Consistent with this immunohistochemical analyses showed a reduced aquaporin-2 labeling in the collecting duct principal cells. Moreover, renal sodium handling was compromised by PUUO evidenced by an increased fractional excretion of sodium which was enhanced by candesartan treatment. In conclusion, our findings suggest that the counterbalance between AT1 receptor-mediated vasoconstriction and NO-mediated vasodilatation which maintain GFR in normal young porcine kidneys is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function.

Tubular function

2015 ◽  
Author(s):  
Marijn Speeckaert ◽  
Joris Delanghe
Keyword(s):  
Fractional Excretion ◽  
Tubular Function ◽  
Tubular Dysfunction ◽  
Renal Fanconi Syndrome ◽  
Glomerular Function ◽  
Diminished Capacity ◽  
Fractional Excretion Of Sodium ◽  
Proximal Tubular ◽  
Pass Through ◽  
Renal Tubular

Assessment of tubular function is more complicated than the measurement of glomerular filtration rate. Different functions may be affecting according to the different segments of tubule involved. Key tests include concentrating and diluting capacity, and fractional excretion of sodium. Tubular proteinuria occurs when glomerular function is normal, but when the proximal tubules have a diminished capacity to reabsorb and to catabolize proteins, causing an increased urinary excretion of the low-molecular-mass proteins that normally pass through the glomerulus. Proximal tubular dysfunction is characterized by hypophosphataemia, and a variety of other abnormalities characteristics of the renal Fanconi syndrome. Distinguishing the location of the lesion in Renal Tubular Acidosis is considered in Chapter 35.

Role of renal interstitial hydrostatic pressure in natriuretic response to ANP

1990 ◽  
Vol 258 (6) ◽  
pp. R1333-R1339 ◽  
Author(s):  
J. Garcia-Estan ◽  
R. J. Roman
Keyword(s):  
Hydrostatic Pressure ◽  
Renal Cortex ◽  
Collecting Duct ◽  
Fractional Excretion ◽  
Interstitial Pressure ◽  
Sodium Potassium ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect ◽  
Distal Delivery

The present study evaluated the role of changes in renal interstitial hydrostatic pressure (RIHP) in the natriuretic response to atriopeptin III (AP III). In control animals, infusion of AP III (100 ng.kg-1.min-1 iv) increased fractional excretion of sodium, potassium, lithium, and water while glomerular filtration rate and renal blood flow were unaltered. The natriuretic response to AP III was associated with a significant elevation in RIHP from 5.6 +/- 0.8 to 8.1 +/- 1.0 mmHg. In rats pretreated with amiloride (1 mg/kg) to block sodium transport in the collecting duct, basal sodium excretion was elevated, but infusion of AP III still increased RIHP and the fractional excretion of sodium, water, and lithium by the same amount as was observed in the control animals. Removal of the renal capsule completely blocked the rise in interstitial pressure in the renal cortex in amiloride-treated rats, but it did not eliminate the elevation in sodium, water, and lithium excretion produced by AP III. To determine whether changes in renal medullary interstitial pressure could play a role in the residual natriuretic response to AP III in these animals, cortical and medullary interstitial pressure were simultaneously measured in rats with a decapsulated kidney. In this group, AP III increased renal medullary interstitial pressure, while cortical interstitial pressure was unaltered. These results are consistent with the view that changes in renal medullary hemodynamics and RIHP contribute to the natriuretic effect of atrial natriuretic peptide by elevating distal delivery of sodium from deep nephrons.

Juxtamedullary nephrons during acute metabolic alkalosis in the rat

1985 ◽  
Vol 249 (1) ◽  
pp. F107-F116
Author(s):  
J. P. Frommer ◽  
D. E. Wesson ◽  
M. E. Laski ◽  
N. A. Kurtzman
Keyword(s):  
Metabolic Alkalosis ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Group Iv ◽  
Renal Handling ◽  
Group Iii ◽  
Contralateral Kidney ◽  
Group I ◽  
Papillary Collecting Duct

The renal handling of bicarbonate during acute metabolic alkalosis was examined in Munich-Wistar rats using micropuncture techniques. Group I received an acute bicarbonate load, and fractional delivery of total CO2 (tCO2) (FDtCO2) to the superficial late distal tubule (LD) was significantly lower than to the base of the papillary collecting duct (B) (18.4 +/- 1.7 vs. 22.9 +/- 1.5%; P less than 0.01), indicating net addition of bicarbonate between LD and B. When acutely bicarbonate-loaded rats had their deep nephrons destroyed with bromoethylamine hydrobromide (BEA) (group II), net addition of tCO2 between LD and B was abolished and net reabsorption uncovered (FDtCO2 LD: 28.0 +/- 3.6 vs. B: 17.5 +/- 2.5%; P less than 0.01). The infusion of amiloride (2.5 mg/kg body wt) to alkalotic rats treated with BEA (group III) completely inhibited distal bicarbonate reabsorption but did not reestablish addition (FDtCO2 LD: 27.6 +/- 1.6 vs. B: 26.1 +/- 3.7%; P = NS). The values obtained for sham-operated animals (group IV) were the same for group I. The patterns that were observed between LD and B were reproduced for the four groups of animals when FDtCO2 LD was compared with the fractional excretion of bicarbonate in the urine of the intact contralateral kidney. These studies suggest that juxtamedullary nephrons contribute a higher load of bicarbonate than superficial nephrons to the final urine during acute metabolic alkalosis in the rat.

Fibroblast growth factor 23 is associated with fractional excretion of sodium in patients with chronic kidney disease

2018 ◽  
Vol 34 (12) ◽  
pp. 2051-2057 ◽  
Author(s):  
Hong Xu ◽  
Ali Hashem ◽  
Anna Witasp ◽  
Rik Mencke ◽  
David Goldsmith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Growth Factor ◽  
Sodium Excretion ◽  
Fibroblast Growth Factor 23 ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Fibroblast Growth ◽  
Fractional Excretion Of Sodium ◽  
Renal Sodium Handling ◽  
Sodium Handling

Abstract Background Recent studies suggest that the phosphaturic hormone fibroblast growth factor 23 (FGF23) is involved in regulation of renal sodium excretion and blood pressure. There is evidence of both direct effects via regulation of the sodium-chloride symporter (NCC) in the distal tubule, and indirect effects through interactions with the renin–angiotensin–aldosterone system. However, clinical data on the association between FGF23 and renal sodium regulation is lacking. Herein, we investigated the associations of FGF23 with renal sodium handling and blood pressure in non-dialysis CKD patients. Methods This was a cross-sectional study encompassing 180 CKD patients Stage 1–5, undergoing renal biopsy. Plasma intact FGF23, 24-h urinary sodium excretion, fractional excretion of sodium (FENa) and blood pressure were measured at baseline. The association between FGF23 and renal sodium handling was explored by multivariate regression analysis. Results The median age was 52.8 years, 60.6% were men and the median estimated glomerular filtration rate (eGFR) was 50.6 mL/min/1.73 m2. In univariate analysis, FGF23 was positively associated with FENa (Spearman’s rho = 0.47; P < 0.001) and systolic blood pressure (rho = 0.17, P < 0.05), but not with plasma sodium, 24-h urinary sodium excretion or mean arterial blood pressure. The association between FGF23 and FENa remained significant after adjustment for potential confounders (multivariable adjusted β coefficient 0.60, P < 0.001). This association was stronger among the 107 individuals with eGFR <60 mL/min/1.73 m2 (β = 0.47, P = 0.04) and in the 73 individuals on any diuretics (β = 0.88, P < 0.001). Adjustment for measured GFR instead of eGFR did not alter the relationship. Conclusions FGF23 is independently associated with increased FENa in non-dialysis CKD patients. These data do not support the notion that FGF23 causes clinically significant sodium retention. Further studies are warranted to explore the mechanism underlying this association.

scholarly journals Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration

2010 ◽  
Vol 299 (3) ◽  
pp. F577-F584 ◽  
Author(s):  
Weidong Wang ◽  
Chunling Li ◽  
Sandra Summer ◽  
Sandor Falk ◽  
Robert W. Schrier
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
Receptor Activation ◽  
Urine Concentration ◽  
At1 Receptor ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Vitro Effect

The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 ± 0.1 in dDAVP+losartan (LSDL) vs. 1.1 ± 0.1 ml·100 g−1·day−1 in dDAVP alone (LSD), P > 0.05] and renal blood flow (6.3 ± 0.5 in LSDL vs. 6.8 ± 0.5 ml/min in LSD, P > 0.05). The urine output, however, was significantly increased in LSDL (2.5 ± 0.2 vs. 1.8 ± 0.2 ml·100 g−1·day−1, P < 0.05) in association with decreased urine osmolality (2,600 ± 83 vs. 3,256 ± 110 mosmol/kgH2O, P < 0.001) compared with rats in LSD. Immunoblotting revealed significantly decreased expression of medullary AQP2 (146 ± 6 vs. 176 ± 10% in LSD, P < 0.01), p-AQP2 (177 ± 13 vs. 214 ± 12% in LSD, P < 0.05), and AQP3 (134 ± 14 vs. 177 ± 11% in LSD, P < 0.05) in LSDL compared with LSD. The expressions of AQP1, the α1- and γ-subunits of Na-K-ATPase, and the Na-K-2Cl cotransporter were not different among groups. In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVP-treated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory.

Dissociation of renal interstitial hydrostatic pressure and natriuresis of atrial natriuretic factor

1990 ◽  
Vol 258 (2) ◽  
pp. R481-R486
Author(s):  
A. A. Khraibi ◽  
D. M. Heublein ◽  
J. C. Burnett ◽  
F. G. Knox
Keyword(s):  
Hydrostatic Pressure ◽  
Atrial Natriuretic Factor ◽  
Wistar Rats ◽  
Fractional Excretion ◽  
Contralateral Kidney ◽  
Time Control ◽  
Natriuretic Factor ◽  
Fractional Excretion Of Sodium ◽  
Male Wistar Rats ◽  
Atrial Natriuretic

The objective of these experiments was to test the hypothesis that renal interstitial hydrostatic pressure (RIHP) plays an important role in the natriuretic effect of atrial natriuretic factor (ANF) in anesthetized Wistar rats. Three groups of male Wistar rats were used in this study. Two groups were infused with different doses of ANF, and the third group was a time control. In all groups, one kidney was acutely decapsulated, and the contralateral kidney was used as control. Renal decapsulation was used to control RIHP. In one group, 3 micrograms.kg-1.h-1 of synthetic ANF were infused intravenously (iv) and produced a plasma level of ANF (PANF) of 810 +/- 186.5 pg/ml. This pharmacological dose of ANF produced a significant increase in RIHP of the control kidney from 9.5 +/- 0.8 to 11.1 +/- 1.3 mmHg (P less than 0.05) but not in the decapsulated kidney [from 7.1 +/- 0.6 to 8.1 +/- 0.9 mmHg, not significant (NS)]. However, the changes in fractional excretion of sodium (FENa) and urine flow rate (V) as a result of ANF infusion were similar in both kidneys. In the decapsulated kidney, FENa and V increased by 1.53 +/- 0.41% and 26.21 +/- 5.98 microliters/min, respectively, from control to ANF infusion periods. In the control kidney, FENa and V increased by 1.60 +/- 0.28% and 31.61 +/- 5.87 microliters/min, respectively, from control to ANF infusion periods. In the second group, 1 microgram.kg-1.h-1 iv of synthetic ANF was infused and produced 165.2 +/- 29.3 pg/ml of PANF.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat

2007 ◽  
Vol 292 (2) ◽  
pp. F655-F659 ◽  
Author(s):  
Sarah Knight ◽  
Harold Snellen ◽  
Michael Humphreys ◽  
Chris Baylis
Keyword(s):  
Volume Expansion ◽  
Fractional Excretion ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Contralateral Kidney ◽  
Fractional Excretion Of Sodium ◽  
Normal Rat ◽  
Renal Clearances ◽  
Natriuretic Effect

Normal rat pregnancy is characterized by plasma volume expansion due to renal sodium retention and is associated with a blunted response to natriuretic stimuli, such as atrial natriuretic peptide (ANP). ANP signals via cGMP, and phosphodiesterases (PDE) inactivate cGMP and terminate the natriuretic response. We previously reported that increased medullary PDE-5 activity occurs in rat pregnancy, which may be the mechanism of the blunted natriuretic effect of ANP. Here, we used anesthetized 16-day pregnant and virgin rats to investigate whether intrarenal infusion of a selective PDE-5 inhibitor, sildenafil, would reverse the blunted response to ANP in pregnancy. We measured blood pressure, renal clearances using inulin and p-aminohippuric acid, and electrolyte excretion at baseline and during an ANP infusion. ANP caused a fall in mean arterial pressure in all groups, and sildenafil induced a further reduction. We observed an increase in sodium excretion with ANP in all rats, but this was blunted in the vehicle-infused pregnant rats. This could not be explained by differences in renal hemodynamics and was of tubular origin, as reflected by the reduced rise in fractional excretion of sodium with ANP in the pregnant rat given vehicle (45 ± 11 vs. 204 ± 49%; P < 0.05). However, intrarenal sildenafil increased the natriuretic response and the rise in fractional excretion of sodium to the virgin value (226 ± 23 vs. 245 ± 73%; not significant), whereas the blunting persisted in the contralateral kidney. This demonstrates that increased intrarenal PDE-5 mediates the blunted natriuretic response to ANP during pregnancy and may contribute to the physiological volume expansion.

Renal responses to angiotensin II receptor blockade in ventilated preterm newborn lambs

1999 ◽  
Vol 11 (8) ◽  
pp. 419
Author(s):  
Lynne M. Smith ◽  
Machiko Ikegami ◽  
Glenda C. Calvario ◽  
James Surdilla ◽  
M. Gore Ervin
Keyword(s):  
Angiotensin Ii ◽  
Feedback Inhibition ◽  
Fractional Excretion ◽  
Extensive Study ◽  
Receptor Blockade ◽  
Activity Levels ◽  
Preterm Newborn ◽  
Angiotensin Ii Receptor ◽  
Fractional Excretion Of Sodium ◽  
Angiotensin Ii Receptor Blockade

Renal and cardiovascular immaturity has been linked with poor outcomes in the premature human newborn. Despite extensive study in the fetus, the contribution of the renin–angiotensin system to renal and cardiovascular function in the premature newborn has not been well characterized. To evaluate the angiotensin II contribution to preterm newborn renal and cardiovascular functions, preterm (120-day) and near-term (136-day) lambs were Caesarean delivered and ventilated. One hour following delivery, animals were randomized to receive angiotensin II receptor-blockade (saralasin; 20 g kg–1 min–1) or saline (CON). Prior to blockade, mean SEM values for urine flow (UFlow), urinary sodium excretion (UNaV), and fractional excretion of sodium (FENa) were similar in all groups. Angiotensin II receptor-blockade decreased Uflow, UNaV and FENa in the 120-day group with no changes in the 136-day animals. No changes in mean arterial pressure, or plasma angiotensin II, aldosterone, and renin activity levels were noted at either gestational age. Conclusions: (1) angiotensin II contributes to the regulation of renal function in 120-day preterm lambs without changing blood pressure and (2) angiotensin II-mediated feedback inhibition of renin release is uncoupled in preterm newborns.

scholarly journals The natriuretic and diuretic response to dopamine is maintained during rat pregnancy

2008 ◽  
Vol 294 (6) ◽  
pp. F1342-F1344 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Chris Baylis
Keyword(s):  
Blood Pressure ◽  
Collecting Duct ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Fractional Excretion ◽  
Sprague Dawley ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Dopamine Infusion ◽  
Fractional Excretion Of Sodium

During pregnancy, there is a marked plasma volume expansion due to renal sodium retention. Pregnant rats exhibit a blunted response to natriuretic stimuli that signal via cGMP, and expression and activity of the cGMP phosphodiesterase PDE-5 are upregulated in the inner medullary collecting duct during pregnancy. Here, we tested the hypothesis that the natriuretic response to a cAMP agonist, dopamine, is maintained during pregnancy. Anesthetized pregnant ( day 16) and age-matched virgin Sprague-Dawley rats were used to determine whether dopamine-cAMP-mediated natriuresis remains intact in pregnant rats. Blood pressure, renal clearances of inulin and p-aminohippuric acid, and excretion of sodium were measured during baseline and dopamine infusion periods. Pregnant rats had a lower blood pressure and hematocrit at baseline than their age-matched virgin counterparts. Dopamine infusion decreased blood pressure and increased glomerular filtration rate and renal plasma flow in virgin but not pregnant rats. Dopamine infusion also increased urine volume, sodium excretion, and the fractional excretion of sodium to a similar extent in virgin and pregnant rats. These results indicate that a cAMP-mediated natriuresis and diuresis (stimulated by dopamine) persists in pregnant rats.

Segment-specific ENaC downregulation in kidney of rats with lithium-induced NDI

2003 ◽  
Vol 285 (6) ◽  
pp. F1198-F1209 ◽  
Author(s):  
Jakob Nielsen ◽  
Tae-Hwan Kwon ◽  
Jeppe Praetorius ◽  
Young-Hee Kim ◽  
Jørgen Frøkiær ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Sodium Intake ◽  
Collecting Duct ◽  
Lithium Treatment ◽  
Fractional Excretion ◽  
Sodium Balance ◽  
Connecting Tubule ◽  
Renal Sodium Excretion ◽  
Fractional Excretion Of Sodium ◽  
Medullary Collecting Duct

Lithium-induced nephrogenic diabetes insipidus is associated with increased renal sodium excretion in addition to severe urinary concentrating defects. However, the molecular basis for this altered renal sodium excretion remains undefined. The amiloride-sensitive sodium channel (ENaC) is expressed in the renal connecting tubule and collecting duct and is essential in renal regulation of body sodium balance and blood pressure. We hypothesized that dysregulation of ENaC subunits may be responsible for the increased sodium excretion associated with lithium treatment. Lithium treatment for 28 days resulted in severe polyuria, increased fractional excretion of sodium, and increased plasma aldosterone concentration. Immunoblotting revealed that lithium treatment induced a marked decrease in the protein abundance of β-ENaC and γ-ENaC in the cortex and outer medulla. Moreover, immunohistochemistry and laser confocal microscopy demonstrated an almost complete absence of β-ENaC and γ-ENaC labeling in cortical and outer medullary collecting duct, which was not affected by dietary sodium intake. In contrast, immunohistochemistry showed increased apical labeling of all ENaC subunits in the connecting tubule and inner medullary collecting duct in rats on a fixed sodium intake but not in rats with free access to sodium. Except for a modest downregulation of the thiazide-sensitive Na-Cl cotransporter, the key renal sodium transporters upstream from the connecting tubule (including the α1-subunit of Na-K-ATPase, type 3 Na/H exchanger, and Na-K-2Cl cotransporter) were unchanged. These results identify a marked and highly segment-specific downregulation of β-ENaC and γ-ENaC in the cortical and outer medullary collecting duct, chief sites for collecting duct sodium reabsorption, in rats with a lithium-induced increase in fractional excretion of sodium.

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